Toluene → Ethyl 1-methyl-5-p-toluoylpyrrole-2-acetate

HRID 1605272Notes

Reaction equation

HRID 1605272 reaction equation
Cl[C:2]([C:4]1[N:8]([CH3:9])[C:7]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:6][CH:5]=1)=[O:3].[C:16]1([CH3:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.CCOCC.C1(C)C=CC([Mg]Br)=CC=1>C1CCCCC1>[CH3:9][N:8]1[C:4]([C:2]([C:19]2[CH:20]=[CH:21][C:16]([CH3:22])=[CH:17][CH:18]=2)=[O:3])=[CH:5][CH:6]=[C:7]1[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

6

Reactant 4

HCID 1140Toluene2×HCID 3283Diethyl Ether2×HCID 21546755Ethyl 5-chlorocarbonyl-1-methylpyrrole-2-acetateHCID 178418370HCID 178418370, compound

Product 1

HCID 11011549Ethyl 1-methyl-5-p-toluoylpyrrole-2-acetateYield 10%

Reagents, catalysts & solvents 1

HCID 8078CyclohexaneSolvent

Conditions

Temperature
-60 °C

Procedure

To a stirred and chilled (-60°C.) solution of 5.0 g. (0.022 mole) of ethyl 5-chlorocarbonyl-1-methylpyrrole-2-acetate in 300 ml. of dry toluene is added in one portion 0.70 g. (0.0044 mole) of anhydrous FeCl3, weighed under 5 ml. of toluene and dissolved in 2 ml. of ether. The freshly prepared Grignard solution of 0.023 mole of p-tolylmagnesium bromide in 15 ml. ether is added dropwise, under hydrogen, to the above reaction mixture at such a rate so as to maintain the reaction temperature at -60 ± 2°C. The mixture is stirred at that temperature for another hour, then hydrolyzed with ice water and made strongly acidic with 3N HCl-ice. The aqueous layer is washed 3 times with benzene and the combined organic layers are washed sequentially with 3-dimethylaminopropylamine-ice, 3N HCl-ice, and saturated NaHCO3 solution. The organic layer is dried over anhydrous MgSO4, filtered and the solvent evaporated off to give about 2.0 g. (20%) of a solid residue with thin layer chromatography (film, silica, 1:3 EtOAo/cyclohexane) showing two major spots (rf - 0.54, 0.90). Column chromatography on 50 g. of CC-4 silica and sequential elution with hexane, hexane-benzene, benzene and benzene-ether gives the desired product (eluted with 10% Et2O/benzene) as an oil (0.75 g., 12% yield). Crystallization from MeOH gives about 350 mg. of a white solid, ethyl 1-methyl-5-(p-toluoyl)pyrrole-2-acetate, m.p. 68°-70°C.

Workup

  1. temperatureto maintain the reaction temperature at -60 ± 2°C
  2. stirringThe mixture is stirred at that temperature for another hour
  3. washThe aqueous layer is washed 3 times with benzene
  4. washthe combined organic layers are washed sequentially with 3-dimethylaminopropylamine-ice, 3N HCl-ice, and saturated NaHCO3 solution
  5. dry with materialThe organic layer is dried over anhydrous MgSO4
  6. filtrationfiltered
  7. customthe solvent evaporated off
  8. customto give about 2.0 g
  9. washof CC-4 silica and sequential elution with hexane, hexane-benzene, benzene and benzene-ether

Sources & evidence

ORD record
ord-a6cf907991f14ca18a0237ef46a7278a
Source dataset
uspto-grants-1976_04
Patent number
US03950355

Reaction notes

Loading…